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Visit https://www.asgct.org/education for more free resources on gene and cell therapy, including progress on a number of promising treatments already in development.

Cocaine addiction is difficult to treat, but with the help of gene therapy, scientists are hoping to change that.

Hosted by: Hank Green

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Sources:
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994240/

https://www.drugabuse.gov/publications/research-reports/cocaine/what-scope-cocaine-use-in-united-states
https://www.drugabuse.gov/publications/research-reports/cocaine/what-treatments-are-effective-cocaine-abusers
https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates

https://www.tandfonline.com/doi/pdf/10.1586/17512433.2.1.1

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Image Sources:
https://commons.wikimedia.org/wiki/File:Protein_BCHE_PDB_1p0i.png
https://upload.wikimedia.org/wikipedia/commons/6/6b/Cocaine-from-xtal-1983-3D-balls.png
https://commons.wikimedia.org/wiki/File:Dopamine_3D_ball.png
https://www.istockphoto.com/vector/dopamine-hypothesis-of-schizophrenia-gm965161994-263433504
https://www.istockphoto.com/vector/cocaine-and-dopamine-gm966271752-263653528
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This episode of SciShow is sponsored by the American Society of Gene and Cell Therapy. [♪ INTRO].

If you’ve heard anything about gene therapy, it’s probably how it can treat certain illnesses and disorders. But while that’s totally true — and amazing — that is not the only way it can be used.

Recently, scientists have been paving the way for gene therapy to be used as a treatment for drug addiction and overdose. Most of these studies have specifically focused on cocaine, and some of the more promising ones suggest that gene therapy might not just be able to treat overdoses… it might also be able to help prevent relapse. This kind of treatment is still very early in the development cycle, but if we can show it safely works in humans, it might just revolutionize the way we treat addiction.

Cocaine is one of the more common illegal drugs out there, and it works by causing large amounts of dopamine to build up in the brain. Dopamine is one of the molecules involved in the body’s reward system, so having a ton of it floating around causes feelings like euphoria. Over time, though, the brain can get used to having all that extra dopamine, which makes the drug hard to permanently quit.

It also means that people need to take more and more of the drug to get the same high. But in large doses, cocaine can be fatal. It can cause irregular heart rhythms, seizures, trouble breathing, or strokes.

And in 2017, there were an estimated 14,000 overdoses in the U. S. involving the drug. There aren’t any great treatments for this addiction, either, although there are plenty in the works.

Many involve changing the brain’s response to chemicals like dopamine. But gene therapy treatments go even deeper. They typically center around a protein called BChE.

It’s made naturally by the liver and breaks down compounds called esters, which sort of “reset” activated neurons and allow muscles to relax. It can be also used to protect people against poisons that disrupt nerve functions, like nerve gas. But it can break down cocaine, too.

The problem is, BChE works way too slowly to treat addictions and overdoses, allowing almost all of a typical dose of cocaine to make it to the brain’s reward centers. So over the years, scientists have been working to modify the protein’s structure so that it’s even faster and more efficient. Using methods like computer simulations, they’ve been pretty successful so far, and some of their modified proteins can inactivate cocaine within seconds of it showing up in the blood.

But there’s still the whole issue of how to deliver the new protein. And that’s where gene therapy really comes in. In this method, scientists specially engineer a virus called a vector, taking out the parts that cause disease and inserting information that tells cells to start making modified BChE.

So far, it hasn’t been tested in humans — most of the work has been in rodent models — but there have been multiple experiments in the last decade, and they’ve generally been really successful. Like, not only does this treatment seem to work, but from what scientists can tell, it also doesn’t seem to have any negative side effects. One of the more significant papers in this field comes from the journal Vaccine in 2014.

In the study, there were two groups of mice. One group was injected with trillions of vector particles that told their bodies to produce an enhanced version of BChE. The other group was either injected with a harmless saline solution or a vector without.

BChE as a control. Based on the team’s special mouse-monitoring system, which looked at things like motor activity and oxygen consumption, the researchers found that the mice didn’t seem to function any different with large amounts of modified BChE in their bodies. But the real test is what happened when those animals were injected with cocaine.

The scientists gave them what would have easily been a lethal dose of the drug, and waited to see what happened. And they found that… like, nothing happened. The mice that received the modified BChE vector didn’t show any changes in activity, which likely meant the protein broke down drug molecules too quickly for them to have any effect.

What’s significant about this treatment isn’t just that it can protect against overdoses, either. It may also be able to help people quit the drug, by preventing someone from feeling its euphoric effects and, therefore, decreasing their drive to use it. In the same 2014 experiment, the scientists found that the levels of modified BChE remained high in the mice’s blood for 8 to 16 months after the initial vector injection.

If those results can be translated to humans, it means that even if someone recovering from addiction does slip up and take the drug, they wouldn’t feel its effects — maybe even years after the treatment. And that would likely help them quit for good. Right now, it’s definitely an “if”, though.

Rodent models of addiction are generally pretty accurate, but they’re not perfect. And researchers want to make sure they’re totally confident that these modified proteins wouldn’t have unexpected effects on the brain. So for now, they’ll keep running tests on animal models to see what happens.

The good news is, experiments with BChE have been effective and safe in everything from rodents to nonhuman primates. So it’s not impossible that these treatments will make their way into human medicine at some point. Also, although it has been a major research area, gene therapy isn't just for cocaine.

Researchers have been studying how to use this technique to treat other addictions, like alcohol or meth. And similar treatments could even be used to fight opioid addictions — although that problem is a bit more complicated, because there are times when people do need strong painkillers. Also, it’s tricky because not all drugs are broken down by BChE, so scientists have to develop different methods for each new addiction.

For example, a 2017 paper actually used gene therapy to enhance the negative effects of drinking, like dizziness, in order to drive mice away from it. Still, even though the exact way of using gene therapy might change from case to case, the tool itself is valuable and has a ton of applications. And if we learn it's safe to start treating addiction this way in humans, it could have the potential to save tens of thousands of lives.

If you’re interested in learning more about developments in this field, or other types of gene therapy and how they work, you can check out the new patient education portal from the American Society of Gene and Cell Therapy. It’s a really comprehensive resource full of clear explanations and easy-to-follow summaries — and it’s all completely free. And to no one’s surprise, we here at SciShow are big fans of free online education around here, especially when the content is as interesting as this.

To check the portal out for yourself, just head over to asgct.org/education, or just follow the link in the description below. [♪ OUTRO].